Biosensors are used for detection of molecules and/or ions, such as protein, drug, DNA, RNA, hormone, glucose, insulin, enzyme, fungus, bacterium, etc., in a biological sample. The sensor can be used for diagnostic application, but for instance also drugs, either therapeutic or abuse, may be detected in for instance blood, urine and saliva.
Such tests are developed to be used in many different settings, e.g. at the point of care for medical applications, or at any desired place for drugs of abuse (DOA), e.g. at the roadside. In all cases a robust, reliable and sensitive device is required, which must also be low cost since it needs to be disposed after the measurement.
Carrying out such a biochemical assay requires a certain degree of fluid handling, at least the sample fluid must be introduced in the sensing device in order to allow binding of the target molecules to the sensor surface. The term fluid refers to a fluidum, and may refer to a liquid, a gas, and a combination thereof. Depending on a kind of assay more or less complicated microfluidic systems are designed. Since a sample is in itself contaminating it must not get in contact with the instrument and must be stored safely inside e.g. a cartridge during and after a measurement.
There has been focus on development of fully integrated microfluidic on chip biochemical systems or lab on chip systems. An issue in these micro fluidic systems is manipulation of fluids from and to different reaction chambers, for which micro actuators such as pumps and valves are typically needed. Pumping and valving can be done in numerous ways, an overview of micro valve concepts is given in Oh & Ahn and a review of micro pumps by Laser & Santiago (K. W. Oh & C. H. Ahn, ‘A review of microvalves’, J. Micromech. Microeng. 16 (2006) R13-R39 and D. J. Laster & J. G. Santiago, ‘A review of micropumps’, J. Micromech. Microeng. 14 (2004) R35-R64).
For integrated cartridges in medical diagnostics or other applications, reliable storage of (bio)chemical reagents is important. For instance, wet reagents may not evaporate and/or leak out while being stored. Some should have no or only limited contact with oxygen or ambient air carrying bacteria and fungi. A valve that is normally closed is preferred. Hence a challenge in microfluidic systems based on active fluid handling using microactuators, i.e. individually addressable valves and pumps, is storage of liquids prior to use of a device, such as a chip or cartridge. To prevent undesired fluid flow and mixing when the chip/cartridge is not addressed, i.e. not in function, reagent chambers need to be sealed. In addition, for long shelf life this sealing must be of high quality, i.e. low permeation of volatile components and no leakage over a long period of time and elevated temperature, while the cartridge is not present in an (analytical) instrument so that powered sealing device cannot be actuated. A further characteristic is that when used these seals should open up easily with means present in the cartridge and instrument. For low cost and complexity it is preferred not to require extra elements, like mechanical piercing or local heating to break the seal, but use the fluid actuation means present for fluid actuation. A known valve or micro-pump is shown in FIG. 1. A diaphragm is closed mechanically by pressing the bottom of the diaphragm into a pressure chamber using an actuator. In a micro-pump the actuator is moved back and forwards. As a valve, it is normally open until closed by the actuator. A problem with such a valve or micro-pump is alignment of the actuator and the pressure chamber or hole (indicated with “1”), especially when there are multiple valves.
Various documents recite valves and use thereof.
US 2010137784 (A1) recites a one-way valve comprising a seat and a membrane having an inner portion that is located over the seat, wherein, in use, the inner membrane portion is selectively deflected from the seat such that a fluid path is created from one side of the membrane to the other so as to open the valve, and wherein an outer peripheral portion of the membrane is stiffer than the inner portion such that the membrane deflection is substantially restricted to only the inner portion. The one-way valve may be used in a pump for an infusion system. This document does not describe a normally closed valve. The membrane is perforated. The valve is dependent on the fluid pressure to actuate the valve. Further, the two-material membrane used is rather complex.
US 2010171054 (A1) recites an integrated microvalve system comprising at least a first fluid branch and a microvalve being controlled by a control pressure in a control channel. The microvalve is adapted to control a fluid flow in the first fluid branch. A flow restrictor arrangement is located between a control port and the control channel to give a pre-determined turn-on and turn-off response characteristics of the microvalve. Preferably the flow restrictor arrangement comprises a deflate channel and an inflate channel arranged in parallel. Each channel comprises a check valve and a flow restrictor, which may have different flow restriction to give different turn-on and turn-off response characteristics for the microvalve.
This document does not describe a normally-closed valve. Inflation and deflation is necessary to operate the valve. The system is not reliable without a power source, e.g. pressure must be maintained adequately to keep the valve shut.
US 2007275455 (A1) describes a valved microfluidics device, microfluidics cell-culture device and system incorporating the devices are disclosed. The valved microfluidics device includes a substrate, a microchannel through which liquid can be moved from one station to another within the device, and a pneumatic microvalve adapted to be switched between open and closed states to control the flow of fluid through a microchannel. The microvalve is formed of three flexible membranes, one of which is responsive to pneumatic pressure applied to the valve and the other two of which deform to produce a more sealable channel cross-section. The cell culture device provides valving to allow controlled loading of cells into the individual well of the device, and exchange of cell-culture components in the wells.
US 2007237686 (A1) recites membrane valves and latching valve structures for microfluidic devices are provided. A demultiplexer can be used to address the latching valve structures. The membrane valves and latching valve structures may be used to form pneumatic logic circuits, including processors.
US 2010151565 (A1) recites a cartridge for the detection of the presence, absence and/or amount of a target nucleotide sequence in a sample comprising one or more nucleic acid sequences. The cartridge comprises a first component and a second component being connectable to each other, the first component comprising at least a first fluid opening and a first sealing surface and the second component comprising at least a second fluid opening and a second sealing surface. Upon connection of the first and second component the first and second fluid opening are in fluid communication and the first and second sealing surfaces are moveable against each other to seal the fluid communication between the first and second fluid opening. The invention is characterized in that the cartridge comprises biasing means for biasing the second sealing surface in the direction of the first sealing surface.
US 2010078584 (A1) recites a valve device comprising a substrate and an elastic membrane, the membrane being joined at least around a valve area to the substrate. The substrate comprises a first channel and a second channel, both ending in the valve area, the first channel having in the valve area a first channel end surface and the second channel having in the valve area a second channel end surface, wherein the area of the first channel end surface is substantially larger than the area of the second channel end surface.
It is a disadvantage of present micro-valves is that these cannot withstand pressures over 1 bar. Also, present micro-valves cannot be used at elevated temperature.